547 research outputs found

    Ovarian dysgerminomas are characterised by frequent KIT mutations and abundant expression of pluripotency markers

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    BACKGROUND: Ovarian germ cell tumours (OGCTs) typically arise in young females and their pathogenesis remains poorly understood. We investigated the origin of malignant OGCTs and underlying molecular events in the development of the various histological subtypes of this neoplasia. RESULTS: We examined in situ expression of stem cell-related (NANOG, OCT-3/4, KIT, AP-2γ) and germ cell-specific proteins (MAGE-A4, NY-ESO-1, TSPY) using a tissue microarray consisting of 60 OGCT tissue samples and eight ovarian small cell carcinoma samples. Developmental pattern of expression of NANOG, TSPY, NY-ESO-1 and MAGE-A4 was determined in foetal ovaries (gestational weeks 13–40). The molecular genetic part of our study included search for the presence of Y-chromosome material by fluorescence in situ hybridisation (FISH), and mutational analysis of the KIT oncogene (exon 17, codon 816), which is often mutated in testicular GCTs, in a subset of tumour DNA samples. We detected a high expression of transcription factors related to the embryonic stem cell-like pluripotency and undifferentiated state in OGCTs, but not in small cell carcinomas, supporting the view that the latter do not arise from a germ cell progenitor. Bilateral OGCTs expressed more stem cell markers than unilateral cases. However, KIT was mutated in 5/13 unilateral dysgerminomas, whereas all bilateral dysgerminomas (n = 4) and all other histological types (n = 22) showed a wild type sequence. Furthermore, tissue from five phenotypic female patients harbouring combined dysgerminoma/gonadoblastoma expressed TSPY and contained Y-chromosome material as confirmed by FISH. CONCLUSION: This study provides new data supporting two distinct but overlapping pathways in OGCT development; one involving spontaneous KIT mutation(s) leading to increased survival and proliferation of undifferentiated oogonia, the other related to presence of Y chromosome material and ensuing gonadal dysgenesis in phenotypic females

    A TDMA scheduler for the AROS architecture

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    Abstract In this paper we present a Time Division Multiple Access (TDMA) scheduler for the Asymmetric communication and ROuting in Sensor networks architecture (AROS). The scheduler enables dynamic network configurations of the AROS architecture. We show that asymmetric multihop communication with dynamic network configurations in AROS prolongs the lifetime of sensor nodes in long distance networks compared to the LEACH architecture

    miR-449 inhibits cell proliferation and is down-regulated in gastric cancer

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    <p>Abstract</p> <p>Background</p> <p>Gastric cancer is the fourth most common cancer in the world and the second most prevalent cause of cancer related death. The development of gastric cancer is mainly associated with <it>H. Pylori </it>infection leading to a focus in pathology studies on bacterial and environmental factors, and to a lesser extent on the mechanistic development of the tumour. MicroRNAs are small non-coding RNA molecules involved in post-transcriptional gene regulation. They are found to regulate genes involved in diverse biological functions and alterations in microRNA expression have been linked to the pathogenesis of many malignancies. The current study is focused on identifying microRNAs involved in gastric carcinogenesis and to explore their mechanistic relevance by characterizing their targets.</p> <p>Results</p> <p>Invitrogen NCode miRNA microarrays identified miR-449 to be decreased in 1-year-old <it>Gastrin </it>KO mice and in <it>H. Pylori </it>infected gastric tissues compared to tissues from wild type animals. Growth rate of gastric cell lines over-expressing miR-449 was inhibited by 60% compared to controls. FACS cell cycle analysis of miR-449 over-expressing cells showed a significant increase in the sub-G<sub>1 </sub>fraction indicative of apoptosis. ß-Gal assays indicated a senescent phenotype of gastric cell lines over-expressing miR-449. Affymetrix 133v2 arrays identified <it>GMNN</it>, <it>MET, CCNE2, SIRT1 </it>and <it>CDK6 </it>as miR-449 targets. Luciferase assays were used to confirm <it>GMNN</it>, <it>MET</it>, <it>CCNE2 </it>and <it>SIRT1 </it>as direct targets. We also show that miR-449 over-expression activated p53 and its downstream target p21 as well as the apoptosis markers cleaved CASP3 and PARP. Importantly, qPCR analyses showed a loss of miR-449 expression in human clinical gastric tumours compared to normal tissues.</p> <p>Conclusions</p> <p>In this study, we document a diminished expression of miR-449 in <it>Gastrin </it>KO mice and further confirmed its loss in human gastric tumours. We investigated the function of miR-449 by identifying its direct targets. Furthermore we show that miR-449 induces senescence and apoptosis by activating the p53 pathway.</p

    Humane Orientation as a New Cultural Dimension of the GLOBE Project: A Validation Study of the GLOBE Scale and Out-Group Humane Orientation in 25 Countries

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    We validate, extend, and empirically and theoretically criticize the cultural dimension of humane orientation of the project GLOBE (Global Leadership and Organizational Behavior Effectiveness Research Program). Theoretically, humane orientation is not just a one-dimensionally positive concept about being caring, altruistic, and kind to others as discussed by Kabasakal and Bodur (2004), but there is also a certain ambivalence to this concept. We suggest differentiating humane orientation toward in-group members from humane orientation toward out-group members. A multicountry construct validation study used student samples from 25 countries that were either high or low in humane orientation (N = 876) and studied their relation to the traditional GLOBE scale and other cultural-level measures (agreeableness, religiosity, authoritarianism, and welfare state score). Findings revealed a strong correlation between humane orientation and agreeableness, welfare state score, and religiosity. Out-group humane orientation proved to be the more relevant subfacet of the original humane orientation construct, suggesting that future research on humane orientation should make use of this measure instead of the vague original scale. The ambivalent character of out-group humane orientation is displayed in its positive correlation to high authoritarianism. Patriotism was used as a control variable for noncritical acceptance of one’s society but did not change the correlations. Our findings are discussed as an example of how rigid expectations and a lack of tolerance for diversity may help explain the ambivalent nature of humane orientatio

    Mass profiles and galaxy orbits in nearby galaxy clusters from the analysis of the projected phase-space

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    We analyze kinematic data of 41 nearby (z<0.1) relaxed galaxy clusters in terms of the projected phase-space density using a phenomenological, fully anisotropic model of the distribution function. We apply the Markov Chain Monte Carlo approach to place constraints on total mass distribution approximated by the universal NFW profile and the profile of the anisotropy of galaxy orbits. We find the normalization of the mean mass-concentration relation is c=6.9_{-0.7}^{+0.6} at the virial mass M_v=5x10^{14}M_sun. Assuming a one-to-one correspondence between sigma_8 and the normalization of the mass-concentration relation in the framework of the concordance model we estimate the normalization of the linear power spectrum to be sigma_8=0.91_{-0.08}^{+0.07}. Our constraints on the parameters of the mass profile are compared with estimates from other methods. We show that galaxy orbits are isotropic at the cluster centres (with the mean ratio of the radial-to-tangential velocity dispersions sigma_r/sigma_theta=0.97+/-0.04) and radially anisotropic at the virial sphere (with the mean ratio sigma_r/sigma_theta=1.75^{+0.23}_{-0.19}). Although the value of the central anisotropy appears to be universal, the anisotropy at the virial radius differs between clusters within the range 1<(sigma_r/sigma_theta)<2. Utilizing the Bautz-Morgan morphological classification and information on the prominence of a cool core we select two subsamples of galaxy clusters corresponding to less and more advanced evolutionary states. It is demonstrated that less evolved clusters have shallower mass profiles and their galaxy orbits are more radially biased at the virial sphere. This property is consistent with the expected evolution of the mass profiles as well as with the observed orbital segregation of late and early type galaxies.Comment: 16 pages, 12 figures, accepted for publication in MNRA

    From representing views to representativeness of views: illustrating a new (Q2S) approach in the context of health care priority setting in nine European countries

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    Governments across Europe are required to make decisions about how best to allocate scarce health care resources. There are legitimate arguments for eliciting societal vales in relation to health care resource allocation given the roles of the general public as payers and potential patients. However, relatively little is known about the views of the general public on general principles which could guide these decisions. In this paper we present five societal viewpoints on principles for health care resources allocation and develop a new approach, Q2S, designed to investigate the extent to which these views are held across a range of European countries. An online survey was developed, based on a previously completed study Q methodology, and delivered between November 2009 and February 2010 across nine countries to 33,515 respondents. The largest proportion of our respondents (44%), were found to most associate themselves with an egalitarian perspective. Differences in views were more strongly associated with countries than with socio-demographic characteristics. These results provide information which could be useful for decision makers in understanding the pluralistic context in which they are making health care resource allocation decisions and how different groups in society may respond to such decisions

    Phenotypic variation of erythrocyte linker histone H1.c in a pheasant (Phasianus colchicus L.) population

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    Our goal was to characterize a phenotypic variation of the pheasant erythrocyte linker histone subtype H1.c. By using two-dimensional polyacrylamide gel electrophoresis three histone H1.c phenotypes were identified. The differently migrating allelic variants H1.c1 and H1.c2 formed either two homozygous phenotypes, c1 and c2, or a single heterozygous phenotype, c1c2. In the pheasant population screened, birds with phenotype c2 were the most common (frequency 0.761) while individuals with phenotype c1 were rare (frequency 0.043)
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